Chaos—definition [from wordnet.princeton.edu]: A state of extreme disorder or confusion.

Consilience—definition [from Wikipedia]: Literally a jumping together of knowledge by the linking of facts and fact-based theory across disciplines to create a common groundwork for explanation.

Lecturing around the country has left us with the powerful impression that both psychiatrists and primary care physicians are hungry for new ways to think about and treat depression and the myriad symptoms and syndromes with which it is associated—including attention deficit disorder, insomnia, chronic pain conditions, substance abuse, and various states of disabling anxiety. Primary care physicians also seem especially excited to learn that depression is not just a psychiatric illness but a behavioral manifestation of underlying pathophysiological processes that promote most of the other conditions they struggle to treat—including cardiovascular disease, diabetes, cancer, and dementia.1,2

In hopes of simultaneously quelling and stimulating this hunger and excitement, this article kicks off a 3–part series that sets forth a new view of major depression that synthesizes multiple converging lines of scientific evidence from an array of fields relevant to mind–body neurobiology. While this new science is fascinating in its own right, our emphasis is to clearly enunciate the promise these new findings hold for improving our ability to diagnose and treat depression and its many comorbidities. We also hope to show that an integrated mind–body view of depression helps explain many aspects of mood disorders that have long been enigmatic. As a result, we hope to enhance our ability to provide our patients with an honest prognosis for their long–term functioning and survival.

We begin with a general discussion of how a mind–body neurobiological approach to depression improves on our current diagnostic understanding of mood and related disorders. In part 2, we will detail the primary elements of a mind–body view of depression; in part 3, we will describe treatment implications that arise from the new science. We will highlight ways in which neurobiological understandings of mood disorders can help us move toward a personalized medicine approach to the treatment of depression and its multiple comorbidities—both psychiatric and medical.

The strange case of Tumor Town, USA

Let’s start with an analogy for major depression…the Strange Case of Tumor Town, USA.

Suppose lots of people in a small town begin coming down with cancerous tumors. Some of these cancers are in the thyroid, some are in the parathyroid, some are in the pituitary, some are in the adrenals, and some are in the pancreas. Some families have multiple members with tumors. Other families in town are completely tumor–free, despite having lived in the town for years. These tumors are more likely to develop in people who move to town than in their kin who live in other places. Not everyone with these tumors dies from them, although having one of these tumors increases one’s risk of an early death. However, whether people live or die, the tumors cause a great deal of anguish.

Now imagine that the government sends scientists and doctors into town to figure out how to treat these cancers. After many meetings and much discussion, these experts reach the following conclusions:

• The tumors that affect different organs probably represent different cancers. Thus, each type of cancer needs a separate name to allow it to be studied in isolation as a unique disease process.

• Because tumors specifically affect the function of the endocrine gland they involve, these glands are probably causing the individual cancers. Therefore, the best course of action is to find genes that are uniquely associated with the functioning of each gland in which tumors have been found.

Given this logic, it is not surprising that it becomes a source of great frustration that so many people have more than 1 of these cancers, either sequentially or at the same time. For example, having a tumor in the thyroid complicates understanding of what a pancreatic or adrenal tumor is doing, and vice versa. Especially when it comes to treatment trials, researchers and clinicians expend a great deal of effort identifying the minority of patients with a tumor in a single location so that they can better understand how to treat each individual illness.